We are requesting funds for the purchase of a High Speed MoFIo Fluorescence Activated Cell Sorter (FACS). Yale University School of Medicine (YSM) is one of the leading sites of immunology research worldwide. Cell sorting is a key technique in immunology and other research, and recent advances are substantially increasing the need for FACS. This, and the growth of our faculty, has made the demand for sorting at YSM vastly outstrip the available resources, as we will document: our current high speed sorter is used >92% of available time and the wait times are four weeks or more for a time slot. In addition, we have had to institute severe rationing of available time slots. These constraints have severely impacted on productivity and the ability to analyze unique biological materials. As only one sample of cells can be sorted at a time on a single machine, throughput is essential. Therefore we request a MoFIo sorter that can process more cells per unit time than all three older sorters at YSM combined. The MoFIo also has important capabilities not available on any other sorter at YSM: ability to sort on 6 or more "colors" at a time and the ability to sort 4 populations simultaneously. These features are important to precisely purify subpopulations of cells and in particular to harvest more than two (the current limit) in a single pass, thus reducing waste and improving the quality of experiments. The strengths of our proposal are: a) well-documented need for the instrument both in terms of capacity and new technology; b) large, productive user base; c) strong track record with the technology; and d) strong institutional support in providing a custom designed new facility for the instrument as well as direct financial support. Twenty-four NIH-funded researchers would benefit from this instrument at YSM. Several young investigators not yet NIH-funded would also benefit. [unreadable] [unreadable] [unreadable]